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INTRODUCTION: Uremic toxins contributing to increased risk of death remain largely unknown. We used untargeted metabolomics to identify plasma metabolites associated with mortality in patients receiving maintenance hemodialysis. METHODS: We measured metabolites in serum samples from 522 Longitudinal US/Canada Incident Dialysis (LUCID) study participants. We assessed the association between metabolites and 1-year mortality, adjusting for age, sex, race, cardiovascular disease, diabetes, body mass index, serum albumin, Kt/Vurea, dialysis duration, and country. We modeled these associations using limma, a metabolite-wise linear model with empirical Bayesian inference, and 2 machine learning (ML) models: Least absolute shrinkage and selection operator (LASSO) and random forest (RF). We accounted for multiple testing using a false discovery rate (pFDR) adjustment. We defined significant mortality-metabolite associations as pFDR < 0.1 in the limma model and metabolites of at least medium importance in both ML models. RESULTS: The mean age of the participants was 64 years, the mean dialysis duration was 35 days, and there were 44 deaths (8.4%) during a 1-year follow-up period. Two metabolites were significantly associated with 1-year mortality. Quinolinate levels (a kynurenine pathway metabolite) were 1.72-fold higher in patients who died within year 1 compared with those who did not (pFDR, 0.009), wheras mesaconate levels (an emerging immunometabolite) were 1.57-fold higher (pFDR, 0.002). An additional 42 metabolites had high importance as per LASSO, 46 per RF, and 9 per both ML models but were not significant per limma. CONCLUSION: Quinolinate and mesaconate were significantly associated with a 1-year risk of death in incident patients receiving maintenance hemodialysis. External validation of our findings is needed.

KEY POINTS: In one hospital-based safety-net dialysis unit, only one half of patients with ESKD knew their cause of kidney failure, which did not differ by English proficiency status. Patients with limited English proficiency (versus English-proficient patients) reported poorer communication with the dialysis care team (less listening, fewer clear explanations, less time spent). We highlight the need for tailored, patient-centered communication between limited English-proficient patients and dialysis care team members. BACKGROUND: ESKD is a chronic health condition for which communication between health care teams and patients is important to guide patient self-management activities. Yet, little is known about the quality of communication among patients with ESKD and their care team members. We examined the influence of patient's limited English proficiency (LEP) status on communication experiences at one dialysis center. METHODS: A survey was administered to adults receiving ESKD care at a dialysis unit within a public health care delivery system between July 2022 and February 2023, to ascertain kidney disease knowledge and perceptions of communication quality with the dialysis care team. Multivariable logistic and ordinal logistic regression models adjusted for age and sex were used to determine associations between LEP status and CKD knowledge. RESULTS: Among 93 eligible patients, 88.2% (n=82) completed the survey. Approximately 37.8% (n=31) had LEP, mean age was 58.8 years, 68.3% were men, mean dialysis vintage was 3.9 years, and 25% had a positive depression screen (LEP 30%; English-proficient 22%). A higher proportion of English-proficient patients screened positive for limited health literacy compared to those with LEP (74.5% versus 38.7%, P = 0.002). Overall, knowledge of assigned cause of ESKD (53.4%) and CKD/transplant knowledge (57.3%) was suboptimal. After adjustment, LEP status was not significantly associated with knowing the correct cause of kidney failure (odds ratio, 0.49; 95% confidence interval, 0.19 to 1.27) but was significantly associated with having a higher score on a CKD/transplant knowledge scale (odds ratio, 3.99; 95% confidence interval, 1.66 to 9.58). Patients with LEP reported poorer communication quality with dialysis providers and staff (less listening, fewer clear explanations, less time spent with patients) compared with English-proficient patients, although differences were not statistically significant. CONCLUSIONS: Overall communication between patients with ESKD and members of the dialysis care team was suboptimal, regardless of English proficiency. Interventions to enhance communication for ESKD patients are needed.

BACKGROUND: Simultaneous urine testing for albumin (UAlb) and serum creatinine (SCr), that is, dual testing, is an accepted quality measure in the management of diabetes. As chronic kidney disease (CKD) is defined by both UAlb and SCr testing, this approach could be more widely adopted in kidney care. OBJECTIVE: We assessed time trends and facility-level variation in the performance of outpatient dual testing in the integrated Veterans Health Administration (VHA) system. DESIGN, SUBJECTS AND MAIN MEASURES: This retrospective cohort study included patients with any inpatient or outpatient visit to the VHA system during the period 2009-2018. Dual testing was defined as UAlb and SCr testing in the outpatient setting within a calendar year. We assessed time trends in dual testing by demographics, comorbidities, high-risk (eg, diabetes) specialty care and facilities. A generalised linear mixed-effects model was applied to explore individual and facility-level predictors of receiving dual testing. KEY RESULTS: We analysed data from approximately 6.9 million veterans per year. Dual testing increased, on average, from 17.4% to 21.2%, but varied substantially among VHA centres (0.3%-43.7% in 2018). Dual testing was strongly associated with diabetes (OR 10.4, 95% CI 10.3 to 10.5, p

RATIONALE & OBJECTIVE: The Kidney Failure Risk Equation (KFRE) predicts the 2-year risk of kidney failure for patients with chronic kidney disease (CKD). Translating KFRE-predicted risk or estimated glomerular filtration rate (eGFR) into time to kidney failure could inform decision making for patients approaching kidney failure. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: CKD Outcomes and Practice Patterns Study (CKDOPPS) cohort of patients with an eGFR40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Our results demonstrate that estimating time to kidney failure in advanced CKD can inform clinical decisions and patient counseling on prognosis, regardless of whether estimates are based on eGFR or the KFRE. PLAIN-LANGUAGE SUMMARY: Clinicians often talk to patients with advanced chronic kidney disease about the level of kidney function expressed as the estimated glomerular filtration rate (eGFR) and about the risk of developing kidney failure, which can be estimated using the Kidney Failure Risk Equation (KFRE). In a cohort of patients with advanced chronic kidney disease, we examined how eGFR and KFRE risk predictions corresponded to the time patients had until reaching kidney failure. Among those with eGFR 40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Estimating time to kidney failure in advanced CKD using either eGFR or KFRE can inform clinical decisions and patient counseling on prognosis.

BACKGROUND: Burnout among clinicians is common and can undermine quality of care, patient outcomes, and workforce preservation, but sources of burnout or protective factors unique to clinicians working in safety-net settings are less well understood. Understanding these clinician experiences may inform interventions to reduce burnout. OBJECTIVE: To describe clinician perspectives on sources of burnout in a safety-net healthcare system. DESIGN: Semi-structured interviews were conducted with clinicians from multiple disciplines who provided care at a safety-net healthcare system from October 2018 to January 2019. Transcripts were analyzed using thematic analysis. PARTICIPANTS: Forty clinicians (25 female and 15 male; mean [SD] age, 41 [9.1]) participated, including physicians, social workers, advanced practice providers, nurses, psychologists, physical and occupational therapists, and other healthcare professionals. MAIN OUTCOMES AND MEASURES: Themes and subthemes that reflected clinician experiences, burnout, and workload expectations. KEY RESULTS: Five themes emerged: limited resources (entrenched social injustices, brokenness of the US healthcare system, precarious discharge options, and revolving door readmissions), barriers to building trust with patients (chasm of communication, addressing fear and mistrust, and being exposed to threats), administrative requirements (criticism hampering meaningful care, assuming extra workloads, bureaucratic burden), compassion fatigue (confronting traumatic situations, persistent worry about patient safety and welfare, witnessing mistreatment and stigmatization, overextending and overinvesting, withdrawing and shutting down, blaming self and career crisis), and advocacy as a counterbalance to burnout (solidarity when helping underserved communities, fervent advocacy, and patient gratitude). CONCLUSIONS: Among clinicians who provide care in a safety-net healthcare system, sources of burnout included limited resources, barriers to building trust with patients, administrative requirements, and compassion fatigue, but clinicians remained driven by their desire to advocate for patients. Policy-level interventions which increase funding to safety-net healthcare systems to bolster existing resources and staffing, create peer-support and wellness programs, and support advocacy efforts may mitigate burnout.

BackgroundInflammation may affect long-term kidney function. Diet may play a role in chronic inflammation. We hypothesized that proinflammatory diets increase the risk of progression to kidney failure with replacement therapy (KFRT), and systemic inflammation is a mediator of the effect of diet on progression to KFRT.MethodsIn the 1988-1994 National Health and Nutrition Examination Survey linked to the national ESKD registry, in adults with CKD (eGFR 15-59 ml/min per 1.73 m2), aged ≥20 years, we calculated the Adapted Dietary Inflammatory Index (ADII) at baseline from a 24-hour dietary recall and an inflammation score (IS) using average of z scores of four inflammation biomarkers. We explored the association of the ADII and IS with risk of incident KFRT using Cox proportional model, adjusting for sociodemographics, physical activity, Framingham risk score, eGFR, and urinary ACR. We evaluated whether, and to what extent, IS mediated the effect of the ADII on KFRT incidence, using causal mediation analysis.ResultsOf 1084 adults with CKD, 109 (10%) developed KFRT. The ADII was associated with increased risk of KFRT (relative hazard [RH] per SD increase (2.56): 1.4 [1.04-1.78]). IS was also associated with KFRT (RH: 1.12; 95% CI, 1.02 to 1.25). Approximately 36% of the association between the ADII and KFRT was explained by IS.ConclusionsAmong adults with CKD, a proinflammatory diet was associated with risk of KFRT, and that association was partially explained by an increase in inflammatory markers. Dietary interventions that reduce inflammation may offer an approach for preventing KFRT.

For persons with proteinuria, angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) are treatment mainstays for reducing kidney disease progression. Guidelines for managing hypertension and chronic kidney disease recommend titrating to the maximum ACEi/ARB dose tolerated. Using deidentified national electronic health record data from the Optum Labs Data Warehouse, we examined ACEi/ARB dosing among adults with proteinuria-defined as either a urine albumin to creatinine ratio of 30 mg/g or greater or a protein to creatinine ratio of 150 mg/g or greater-who were prescribed an ACEi/ARB medication between January 1, 2017, and December 31, 2018. Among 100,238 included patients (mean age, 65.1 years; 49,523 [49.4%] female), 29,883 (29.8%) were taking maximal ACEi/ARB doses. Among 74,287 patients without potential contraindications to dose escalation (systolic blood pressure

BackgroundIn chronic kidney disease (CKD), assessment of both estimated glomerular filtration rate (eGFR) and albuminuria are necessary for stratifying risk and determining the need for nephrology referral. The Kidney Disease: Improving Global Outcomes clinical practice guidelines for CKD recommend nephrology referral for eGFR

RATIONALE & OBJECTIVE: Equations for estimated glomerular filtration rate (eGFR) that incorporate a term for race assign a higher value to Black individuals compared to non-Black individuals for the same sex, age, and serum creatinine concentration. This difference may contribute to racial disparities in kidney transplant access. We sought to (1) compare time from meeting a transplant eligibility threshold of eGFR ≤20 mL/min/1.73 m2 to kidney failure with replacement therapy (KFRT) among Black, Hispanic, and White patients, and (2) assess the impact of incorporation of race into eGFR expressions on establishment of waitlist eligibility and time from eligibility to KFRT. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: Using the OptumLabs Data Warehouse, we assembled a cohort of 40,042 White, 8,519 Black, and 3,569 Hispanic patients having at least one eGFR value between 20 and 60 mL/min/1.73 m2 within the preceding 2 years and an incident outpatient eGFR of ≤20 mL/min/1.73 m2 between 2008-2018, using the CKD-EPI creatinine equation that includes a term for race coded as Black or non-Black. We then reassembled a Black patient cohort based on incident eGFR ≤20 mL/min/1.73 m2 (n = 11,269) estimated using the same CKD-EPI equation but coding Black patients as non-Black. EXPOSURE: Race/ethnicity. OUTCOME: Time to KFRT. ANALYTICAL APPROACH: Unadjusted and adjusted Fine-Gray models; linear regression to compute eGFR slopes. RESULTS: By 3 years, the cumulative incidence of KFRT was 20.5% among White patients, 40.9% among Hispanic patients, 36% among Black patients whose GFR was estimated using a race term coded as Black, and 28.7% among Black patients whose GFR was estimated using a race term coded as non-Black. In fully adjusted analyses including 11,269 Black patients with an eGFR ≤20 mL/min/1.73 m2 based on coding them as non-Black, KFRT risk remained greater among Black (HR, 1.28 [95% CI, 1.15-1.43]) and Hispanic (HR, 1.66 [95% CI, 1.18-2.31]) patients than among White patients. Based on slopes of eGFR decline, coding Black patients as non-Black would allow earlier waitlist activation by an estimated median of 0.5 [interquartile range, 0.27-1.23] years. LIMITATIONS: Inability to exclude individuals who would not be kidney transplant candidates if comprehensively evaluated. CONCLUSIONS: A uniform eGFR threshold provides less opportunity for being placed on the transplant waitlist among Black and Hispanic patients. For many Black patients, estimation of GFR as if their race category were non-Black would allow substantially earlier waitlisting but would not eliminate their shorter time to KFRT and reduced opportunity for preemptive transplantation compared with White patients.

BackgroundNeighborhood social cohesion (NSC) is the network of relationships as well as the shared values and norms of residents in a neighborhood. Higher NSC has been associated with improved cardiovascular health, largely among Whites but not African Americans. In a bi-racial cohort, we aimed to study the association between NSC and chronic disease awareness and engagement in healthy self-management behaviors, two potential mechanisms by which NSC could impact cardiovascular health outcomes.MethodsUsing the Healthy Aging in Neighborhoods of Diversity Across the Lifespan Study (HANDLS), we cross-sectionally examined the association between NSC and awareness of three chronic conditions (diabetes, chronic kidney disease (CKD), and hypertension) and engagement in healthy self-management behaviors including physical activity, healthy eating, and cigarette avoidance.ResultsStudy participants (n = 2082) had a mean age of 56.5 years; 38.7% were White and 61.4% African American. Of the participants, 26% had diabetes, 70% had hypertension and 20.2% had CKD. Mean NSC was 3.3 (SD = 0.80) on a scale of 1 (lowest score) to 5 (highest score). There was no significant association between NSC and any chronic disease awareness, overall or by race. However, each higher point in mean NSC score was associated with less cigarette use and healthier eating scores, among Whites (adjusted odds ratio [aOR], 95% confidence interval [CI]: =0.76, 0.61-0.94; beta coefficient [βc]:, 95% CI: 1.75; 0.55-2.97, respectively) but not African Americans (aOR = 0.95, 0.79-1.13; βc: 0.46, - 0.48-1.39, respectively; Pinteraction = 0.08 and 0.06). Among both Whites and African Americans, higher NSC scores were associated with increases in self-reported physical activity (βc: 0.12; 0.08-0.16; Pinteraction = 0.40).ConclusionsCommunity engagement and neighborhood social cohesion may be important targets for promotion of healthy behaviors and cardiovascular disease prevention. More research is needed to understand the different associations of NSC and healthy behaviors by race.

BackgroundCurrent equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.MethodsWe developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations.ResultsIn the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks.ConclusionsNew eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Background: Burnout among clinicians is common and can undermine quality of care, patient outcomes, and workforce preservation, but sources of burnout or protective factors unique to clinicians working in safety-net settings are less well understood. Understanding these clinician experiences may inform interventions to reduce burnout. Objective: To describe clinician perspectives on sources of burnout in a safety-net healthcare system. Design: Semi-structured interviews were conducted with clinicians from multiple disciplines who provided care at a safety-net healthcare system from October 2018 to January 2019. Transcripts were analyzed using thematic analysis. Participants: Forty clinicians (25 female and 15 male; mean [SD] age, 41 [9.1]) participated, including physicians, social workers, advanced practice providers, nurses, psychologists, physical and occupational therapists, and other healthcare professionals. Main Outcomes and Measures: Themes and subthemes that reflected clinician experiences, burnout, and workload expectations. Key Results: Five themes emerged: limited resources (entrenched social injustices, brokenness of the US healthcare system, precarious discharge options, and "revolving door" readmissions), barriers to building trust with patients (chasm of communication, addressing fear and mistrust, and being exposed to threats), administrative requirements (criticism hampering meaningful care, assuming extra workloads, bureaucratic burden), compassion fatigue (confronting traumatic situations, persistent worry about patient safety and welfare, witnessing mistreatment and stigmatization, overextending and overinvesting, withdrawing and shutting down, blaming self and career crisis), and advocacy as a counterbalance to burnout (solidarity when helping underserved communities, fervent advocacy, and patient gratitude). Conclusions: Among clinicians who provide care in a safety-net healthcare system, sources of burnout included limited resources, barriers to building trust with patients, administrative requirements, and compassion fatigue, but clinicians remained driven by their desire to advocate for patients. Policy-level interventions which increase funding to safety-net healthcare systems to bolster existing resources and staffing, create peer-support and wellness programs, and support advocacy efforts may mitigate burnout. [ABSTRACT FROM AUTHOR]

In their article, Siddique and colleagues report a systematic review of literature relevant to the question of the benefits and risks of incorporating race into clinical algorithms. The editorialist discusses the findings and the gaps in knowledge to guide decisions about factors that improve clinical algorithms and do not foster health disparities. [ABSTRACT FROM AUTHOR]